title: Mothers' prenatal stress and their children's antisocial outcomes--a moderating role for the dopamine D4 receptor (DRD4) gene.
abstract: BACKGROUND
  Maternal distress during pregnancy has been linked to aggressive behavior in offspring. This effect has been interpreted in terms of 'fetal programming'. The 7-repeat (7r) allele of a VNTR polymorphism in exon III of the human dopamine receptor D4 (DRD4) has consistently been associated with externalizing behavior problems, especially in the presence of adverse environmental factors. So far, it is not known whether the DRD4 genotype moderates the effect of prenatal maternal stress on the development of childhood antisocial behavior.
  
  
  METHODS
  As part of an ongoing epidemiological cohort study, prenatal maternal stress was assessed using self-report 3 months following child birth. When children were 8, 11, and 15 years old, mothers rated their children's externalizing behavior, and diagnoses of conduct disorder and/or oppositional defiant disorder (CD/ODD) according to DSM-IV were obtained. In a sample of N = 308 participants, the effects of the DRD4 genotype, prenatal maternal stress, and the interaction thereof on antisocial outcome were tested.
  
  
  RESULTS
  Under conditions of elevated prenatal maternal stress, children carrying one or two DRD4 7r alleles were at increased risk of a diagnosis of CD/ODD. Moreover, homozygous carriers of the DRD4 7r allele displayed more externalizing behavior following exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD4 4r allele turned out to be insensitive to the effects of prenatal stress.
  
  
  CONCLUSIONS
  This study is the first to report a gene-environment interaction related to DRD4 and prenatal maternal stress using data from a prospective study, which extends earlier findings on the impact of prenatal maternal stress with respect to childhood antisocial behavior.
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Zohsel
authors.forename: Arlette F
authors.initials: AF
authors.lastname: Buchmann
authors.forename: Dorothea
authors.initials: D
authors.lastname: Blomeyer
authors.forename: Erika
authors.initials: E
authors.lastname: Hohm
authors.forename: Martin H
authors.initials: MH
authors.lastname: Schmidt
authors.forename: Günter
authors.initials: G
authors.lastname: Esser
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Manfred
authors.initials: M
authors.lastname: Laucht
mesh_terms: D000293:Adolescent; D000328:Adult; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D002648:Child; D019955:Conduct Disorder / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009035:Mothers / Q000523:psychology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D011446:Prospective Studies; D050638:Receptors, Dopamine D4 / Q000145:classification / Q000235:genetics*; D013315:Stress, Psychological / Q000150:complications* / Q000453:epidemiology
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4
keywords: DRD4; Prenatal stress; antisocial; conduct disorder; gene-environment interaction